Regioselective catalytic conversion of hydrocarbons to versatile synthetic reagents via C-H bond functionalization

ABSTRACT

The present invention provides a novel and improved method of functionalizing a C—H bond of an arene compound comprising the step of reacting an organometallic compound having a group 14 element with the arene compound having at least one hydrogen bonded to a carbon in the presence of a catalyst.

RELATED APPLICATIONS

This application claims benefit under 35 U.S.C., §119(e) to U.S.Provisional application No. 61/344,047 filed on May 13, 2010.

SCOPE OF THE INVENTION

The present invention relates to a novel and improved method forcatalytic functionalization of a C—H bond. More particularly, thepresent invention relates to a novel and improved method offunctionalizing a C—H bond of an arene compound having at least onehydrogen bonded to a carbon, the method comprising a single step ofreacting the arene compound with an organometallic compound having agroup 14 element.

BACKGROUND OF THE INVENTION

Methods of forming a C—C bond between two different compounds eachhaving a C—H bond continues to be of keen interest to the pharmaceuticaland fine chemical industries. Namely, the formation of the C—C bond byfirst breaking the two C—H bonds and then forming a bond between the twocarbons is particularly desirable given ready accessibility ofhydrocarbon compounds, atom efficiency, and reduced production cost. Theformation of the C—C bond may be illustrated by the following chemicalequation:R₁—C—H+H—C—R₂→R₁—C—C—R₂

Methods of forming C—C bonds from C—H bonds are known to be difficult asC—H bonds are only modestly reactive under mild conditions. One way toovercome the difficulty is to introduce an intermediate step of firstfunctionalizing or “activating” the C—H bond using a transition metalcatalyst and then reacting the functionalized C—H bond with anothercompound. Functionalization of the C—H bond involves substituting thehydrogen atom with a different functional group. Preferably, thefunctional group forms a more reactive bond with the carbon such thatthe carbon becomes more reactive to form different chemical bonds insubsequent reactions.

To date, functionalization of C—H bonds have focused primarily onformation of C—B, C—C, C—N, and C—O bonds with much less attention paidto coupling the carbon to heavier atoms. For example, one of the mostcommonly used methods involves formation of a C—B bond by use of boronchemistry. The “functionalized” C—B bond may subsequently be utilized ina Imamura-Suzuki coupling reaction to create a C—C bond as exemplifiedin the following chemical equation where each of R₁ and R₂ comprises ahydrocarbon moiety:

The foregoing use of boron chemistry to create the C—C bond suffers anumber of disadvantages including low product yields and limited scopeof application, especially in the presence of incompatible functionalgroups. It is therefore desirable to have a new and improved method tofunctionalize a C—H bond which avoids the disadvantages of boronchemistry.

It is of note that a new and improved method to functionalize a C—H bondwould have valuable applications in synthesis of fluorinated compounds.Fluorinated compounds are considered to be important compounds in thepharmaceutical and agrochemical sectors due to their increasedresistance to metabolic degradation and increased lipophilicity.Fluorinated compounds also find use as important parts in a number ofpolymers, membrane, and semi-conductor materials.

Traditionally, to synthesize a particular fluorinated compound,fluorination is performed at a final stage of chemical synthesis toconvert a non-fluorinated intermediate to the desired fluorinatedcompound. Such approach suffers the disadvantages of being limited bythe chemistry of fluorination and the high costs associated withfluorination. Therefore, it would be advantageous to instead begin thesynthesis with a fluorinated intermediate, and then subject thefluorinated intermediate to subsequent reactions to obtain the desiredfluorinated compound. Such approach is particularly advantageous as anumber of fluorinated intermediates or starting compounds arecommercially available.

To synthesize the desired fluorinated compound from the fluorinatedintermediate, the subsequent reactions may advantageously incorporatefunctionalization of a C—H bond of the fluorinated intermediate. Forexample, the C—H bond may be functionalized and converted to a C—Snbond. The carbon of the C—Sn bond may subsequently be utilized in awell-developed Stille coupling reaction to form a bond with anothercarbon as exemplified in the following chemical reaction where each of Rand R′ comprises a hydrocarbon moiety:R—Sn(R)₃+R′—X→R—R′+X—Sn(R)₃Such combination of functionalization of a C—H bond and subsequentreaction of the functionalized bond to form a C—C bond may readily beincorporated as part of synthesis of a wide variety of commerciallyuseful fluorinated compounds.

Currently, a number of fluorinated intermediate compounds with afunctionalized C—Sn bond are commercially available. Such compoundsinclude 2,3,4,5,6-pentafluorophenyltrimethylstannane andbis(pentafluorophenyl)dimethylstannane. Other fluorinated intermediatecompounds such as 2,3,5,6-tetrafluorophenyltrimethylstannane,2,3,4,6-tetrafluorophenyltrimethylstannane, and(2,3,4-trifluorophenyl)trimethylstannane are known but are notcommercially available on any reasonable scale. Such fluorinatedcompounds are often made using methods that are expensive (and involvinguse of organomagnesium, organolithium and organotinhalide compounds),leads to a limited range of products, and which involve multiple stepsperformed at high temperatures with poor product yield.

Therefore, it is desirable to find a novel and improved method tosynthesize fluorinated intermediate compounds with a functionalized C—Snbond, which is simple and commercially viable with high product yieldsand which avoids use of expensive and harmful reagents.

SUMMARY OF THE INVENTION

The applicant having conducted extensive studies and research haveunexpectedly discovered that a C—H bond of an arene compound may beselectively functionalized by reaction with an organometallic compoundhaving a group 14 element. Particularly, the applicant has unexpectedlydiscovered that a C—H bond of a fluorinated compound could befunctionalized in a single step without also functionalizing the C—Fbonds.

It is therefore an object of the present invention is to provide a noveland improved method of functionalizing a C—H bond of an organiccompound, which overcomes the disadvantages noted above, and which maybe performed in a relatively straightforward manner in a single stepusing commercially available compounds and requiring lower energy inputand costs.

A further object of the present invention is to provide a novel andimproved method of functionalizing a C—H bond of an organic compoundpreferably an aromatic compound and more preferably a fluorinatedaromatic compound, which avoids use of organomagnesium, organolithiumand organotinhalide compounds, and to minimize harmful reactionintermediates or by-products.

A further object of the present invention is to provide a novel andimproved method for functionalizing a C—H bond of a fluorinated organicor arene compound, which is readily incorporated into multi-stepsynthesis for a wide variety of fluorinated organic or arene compounds,and which avoids the limitation of fluorination chemistry and associatedhigh costs.

A further object of the present invention is to provide a novel andimproved method of functionalizing a C—H bond of an organic compound byformation of a C—Sn bond, which is readily utilized in a Stille couplingreaction to form a C—C bond with greater yield and wider applicationwhen compared to Imamura-Suzuki coupling reaction.

In one simplified aspect, the invention provides a novel and improvedmethod of functionalizing a C—H bond of an arene compound, and morepreferably a fluorinated arene compound, comprising the step of reactinga first organometallic compound with the arene compound in the presentof a catalyst, wherein said first organometallic compound comprises agroup 14 element, and said arene compound comprises at least onehydrogen bonded to a carbon.

Preferably, the first organometallic compound is an organotin compound.The organotin compound may have but not limited to the chemical formulaR₃SnR¹, wherein each of R and R¹ comprises a functional group or moiety.The R group may preferably be but not limited to a methyl group (Me) ora butyl group (Bu). The R¹ group may preferably be but not limited to avinyl group or a propenyl group which may include a functional group ormoiety attached thereto. Good reactivity and high product yields havebeen demonstrated with the organotin compound of formula R₃SnR¹, whereinthe R group is a methyl or butyl group and R¹ group is a vinyl orpropenyl group, or namely Me₃Sn(CH═CH₂), Bu₃Sn(CH═CH₂), Me₃Sn(CH═CHCH₃)and Bu₃Sn(CH═CHCH₃). Bu₃Sn(CH═CH₂) is particularly preferred in themethod of the present invention due to its commercial availability.

Alternatively, the first organometallic compound may preferably be anorganosilane compound. The organosilane compound may have but notlimited to the chemical formula R² ₃SiR³, wherein each of R² and R³comprises a functional group or moiety. The method of the presentinvention has been demonstrated to work with the preferred R² such as aphenyl group, a hydrogen or any combinations thereof, and the preferredR³ such as a hydrogen.

Alternatively, the reagent may also preferably be an organogermaniumcompound or an organolead compound.

The arene compound may be a heterocyclic compound. Preferredheterocyclic compounds include pyridine, pyrazine, imidazole, pyrazole,oxazole, and thiophene. More preferably, the arene compound comprise abenzene. Most preferred arene compounds include fluorinated benzenessuch as fluorobenzene, 1,2-difluorobenzene, 1,3-difluorobenzene,1,4-difluorobenzene, 1,2,3-trifluorobenzene, 1,2,4-trifluorobenzene,1,3,5-trifluorobenzene, 1,2,3,4-tetrafluorobenzene,1,2,3,5-tetrafluorobenzene, 1,2,4,5-tetrafluorobenzene, andpentafluorobenzene. As well, more reactive fluorinated benzenes, such as1,3-difluorobenzene, 1,2,4-trifluorobenzene, 1,3,5-trifluorobenzene,1,2,3,5-tetrafluorobenzene, 1,2,4,5-tetrafluorobenzene, andpentafluorobenzene, which has a hydrogen substituent adjacent to twofluorine substituents, are more particularly preferred.

Preferably, the arene compound comprises a substituent other thanhydrogen. The substituent may include but not limited to a fluorine, atrifluoromethyl group and other directing groups. The method of thepresent invention has been demonstrated to work with a number offluorinated arene compounds.

The catalyst is not particularly limited, and is selected to be capableof catalyzing functionalization of the C—H bond of the arene compound.Preferably, the catalyst comprises at least one of a secondorganometallic compound and an ancillary ligand. The ancillary ligandmay be a chelating ligand or a multidentate ligand, and are preferablyselected from PCy₃, P^(i)Pr₃, PEt₃ and MeNC₅H₄N^(i)Pr, wherein Cy is acyclohexyl group, Et is an ethyl group and ^(i)Pr is a isopropyl group.The structural formula of the aforementioned MeNC₅H₄N^(i)Pr is shownbelow:

Most preferably, the catalyst is Ni(COD)₂, where COD is1,5-cyclooctadiene. Ni(COD)₂ either alone or in combination with atleast one of PCy₃, P^(i)Pr₃, PEt₃ and MeNC₅H₄N^(i)Pr as the ancillaryligand is most preferred.

The method of the present invention may be performed neat or in asolvent. The solvent may preferably be an organic solvent including butnot limited to pentane, benzene and toluene. The temperature of themethod of the present invention is not particularly limited butpreferably performed under 100° C., and most preferably between 25° C.to 45° C. The pressure to be used in the method of the present inventionis also not particularly limited. Conveniently, the method may becarried out in a sealed NMR tube.

The method of the present invention is not particularly limited withrespect to the relative amounts of the first organometallic compound,the arene compound, and the catalyst. Preferably, the catalyst is addedin an amount which is 1 to 10 percent of the molar amount of either thefirst organometallic compound or the arene compound. More preferably,the amount of the catalyst is between 3 to 8 percent of the molar amountof either the first organometallic compound or the arene compound.

The method of the present invention may be used to functionalize morethan one C—H bonds of the arene compound if the arene compound containsmore than one C—H bonds. To functionalize more than one C—H bonds of thearene compound, for example two C—H bonds, it is preferable to performthe method with the first organometallic compound in an amount which istwice or more of the molar amount of the arene compound. Tofunctionalize for example three C—H bonds, it is preferable to performthe method with the first organometallic compound in an amount which isthree times or more of the molar amount of the arene compound.

Another aspect of the present invention therefore provides a method offunctionalizing a C—H bond of an arene compound comprising the step ofreacting a first organometallic compound with said arene compound in thepresent of a catalyst, wherein said first organometallic compoundcomprises a group 14 element; and said arene compound comprises at leastone hydrogen bonded to a carbon.

In a further aspect of the present invention, the method is carried outin a single step.

In a further aspect of the present invention, said first organometalliccompound is selected from the group consisting of an organotin compound,an organosilane compound, an organogermanium compound and an organoleadcompound.

In yet a further aspect of the present invention, said organotincompound has the chemical formula R₃SnR¹, wherein each of said R isselected from the group consisting of a methyl group and a butyl group;and said R¹ comprises a double bond.

In a further aspect of the present invention, said double bond isadjacent to a bond between said R¹ and said Tin.

In a further aspect of the present invention, said R¹ is selected fromthe group consisting of a vinyl group and a propenyl group.

In a further aspect of the present invention, said organotin compound isselected from the group consisting of Me₃Sn(CH═CH₂), Bu₃Sn(CH═CH₂),Me₃Sn(CH═CHCH₃) and Bu₃Sn(CH═CHCH₃), wherein said Me is the methyl groupand said Bu is the butyl group.

In a further aspect of the present invention, said organosilane compoundhas the chemical formula R² ₃SnH, wherein each of said R² is selectedfrom the group consisting of a phenyl group and a hydrogen.

In a further aspect of the present invention, said arene compound is aheterocyclic compound.

In a further aspect of the present invention, said arene compound has asa substituent a fluorine.

In a further aspect of the present invention, said arene compound isbenzene.

In a further aspect of the present invention, said benzene has as asubstituent a fluorine.

In a further aspect of the present invention, said hydrogen is adjacentto two of said fluorine.

In a further aspect of the present invention, said benzene is selectedfrom the group consisting of 1,2-difluorobenzene, 1,3-difluorobenzene,1,4-difluorobenzene, 1,2,3-trifluorobenzene, 1,2,4-trifluorobenzene,1,3,5-trifluorobenzene, 1,2,3,4-tetrafluorobenzene,1,2,3,5-tetrafluorobenzene, 1,2,4,5-tetrafluorobenzene, andpentafluorobenzene.

In a further aspect of the present invention, said catalyst comprises atleast one of a second organometallic compound and an ancillary ligand.

In a further aspect of the present invention, said second organometalliccompound comprises an element selected from the group consisting ofnickel and mercury.

In a further aspect of the present invention, said ancillary ligandcomprises at least one of PCy₃, P^(i)Pr₃, PEt₃ and MeNC₅H₄N^(i)Pr,wherein said Cy is a cyclohexyl group; said ^(i)Pr is a isopropyl group;said Et is an ethyl group; said Me is a methyl group; and saidMeNC₅H₄N^(i)Pr has the following structural formula:

In a further aspect of the present invention, said second organometalliccompound comprises Ni(COD)₂, wherein COD is 1,5-cyclootadiene.

In a further aspect of the present invention, said step is carried outwith a first molar amount of said reagent and a second molar amount ofsaid organic compound, wherein said first molar amount isstoichiometrically equivalent to said second molar amount.

In a further aspect of the present invention, said first molar amount isgreater than said second molar amount.

In a further aspect of the present invention, said first molar amount isless than said second molar amount.

In a further aspect of the present invention, said step is carried outat a temperature lower than 100° C.

In a further aspect of the present invention, said temperature isbetween 25° C. to 45° C.

In a further aspect of the present invention, said step is carried outin an organic solvent selected from the group consisting of pentane,benzene, and toluene.

In a further aspect of the present invention, said step is carried outwithout solvent.

BRIEF DESCRIPTION OF THE DRAWINGS

Reference may now be had to the following detailed description, takentogether with the accompanying drawings, in which:

FIG. 1 illustrates the chemical equations of the most preferred methodsof the present invention, which involves mono-functionalization of aflourinated benzene or pyridine containing 1 to 5 fluorine substituentswith Bu₃Sn(CH═CH₂) in the presence of a catalyst.

FIG. 2 illustrates the chemical equations of the most preferred methodsof the present invention, which involves both mono-functionalization anddi-functionalization of a fluorinated benzene containing 2 to 4 fluorinesubstituents with Bu₃Sn(CH═CH₂) in the presence of a catalyst.

FIG. 3 illustrates examples of two different possible reactionmechanisms for the specific preferred method of functionalization ofC₆F₅D with cis-(1-propenyl)SnBu₃ in the presence of a catalyst.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The most preferred embodiments of the present invention are henceforthdescribed with reference to FIGS. 1 to 3. The most preferred embodimentsare provided as mere examples which are in no way intended to limit thescope of the present invention. It will be readily apparent to a personskilled in the art that variations and modifications may be made to themost preferred embodiments within the scope of the present invention.

In a first example process, a single-step catalytic stannylation of afluorinated arene compound was achieved using Bu₃Sn(CH═CH₂) orMe₃Sn(CH═CH₂) as a first organometallic compound in the presence ofNi(COD)₂ with at least one of MeNC₅H₄N^(i)Pr and P^(i)Pr₃ as a catalystas follows:

The preferred reaction advantageously shows quantitativefunctionalization and may be performed using as little as 1 mol % ofNi(COD)₂ and MeNC₅H₄N^(i)Pr to go to completion. Test reactions were runat room temperature and yielded ethylene as a by-product. The reactionmay further be performed without addition of solvent.

In test samples the above reaction has been demonstrated to work with anumber of different fluorinated arene compounds yielding resultingfunctionalized products in excess of 90%.

Table 1 below illustrates example single-step reactions of the presentinvention involving use of fluorinated arene compounds having 2 to 5fluorine substituents, the catalyst Ni(COD)₂ and the ancillary ligandMeNC₅H₄N^(i)Pr and/or P^(i)Pr₃. The yield percent marked with thesuperscript a provides NMR yield from integration of ¹⁹F[¹H] NMRspectra, and yield percent marked with the superscript b providesisolated yield after chromatography. The condition hours marked with thesuperscript c and d denote that the reaction was carried out using 2.5molar amount of Bu₃Sn(CH═CH₂) and 10 fold excess of the fluorinatedarene compound, respectively.

TABLE 1 Ancillary Ligand and Ni(COD), Yield Reagent Loading (%)Conditions (%) Products # C₆F₆H MeNC₅H₄N^(i)Pr 3% P^(i)Pr₃, 5% 35° C., 1h 80° C., 3 h 95^(a) (70^(b)) 98^(a)

 1 1,2,4,5-C₆F₄H₂ MeNC₅H₄N^(i)Pr 3% P^(i)Pr₃, 5% 35° C., 0.5 h 80° C.,0.2 h 95^(a) (4^(a) of 3) 93^(a) (7^(a) of 3)

 2 1,2,4,5-C₆F₄H₂ MeNC₅H₄N^(i)Pr 3% P^(i)Pr₃, 5% 45° C., 6 h^(c) 80° C.,8 h^(c) 85^(a) (11 of 2) 99^(a)

 3 1,2,3,5-C₆F₄H₂ MeNC₅H₄N^(i)Pr 3% P^(i)Pr₃, 5% 35° C., 0.7 h 80° C.,0.5 h 95^(a) (82^(b)) 90^(a) (10 of 5)

 4 1,2,3,5-C₆F₄H₂ MeNC₅H₄N^(i)Pr 5% P^(i)Pr₃, 5% 40° C., 18 h^(c) 80°C., 12 h^(c) 84^(a) (12 of 4) 99^(a)

 5 1,2,3,4-C₆F₄H₂ MeNC₅H₄N^(i)Pr 3% P^(i)Pr₃, 5% 45° C., 12 h 80° C., 4h 38^(a) 95^(a)

 6 1,2,4-C₆F₄₃H₂₃ MeNC₅H₄N^(i)Pr 3% P^(i)Pr₃, 5% 35° C., 7 h 80° C., 1 h98^(a) 98^(a)

 7 1,2,4-C₆F₄₃H₂₃ P^(i)Pr₃, 5% 80° C., 48 h^(c) 50^(a) (40^(a) of 7 andBu₆Sn₂)

 8 1,3,5-C₆F₄₃H₂₃ MeNC₅H₄N^(i)Pr 3% P^(i)Pr₃, 5% 40° C., 4 h 80° C., 0.5h 91^(a) (83^(b)) 83^(a) (17 of 11)

10 1,3,5-C₆F₄₃H₂₃ MeNC₅H₄N^(i)Pr 5% P^(i)Pr₃, 5% 40° C., 18 h^(c) 80°C., 12 h^(c) 38^(a) (55 of 10 ) 45^(a) (50 of 12)

11 1,3,5-C₆F₄₃H₂₃ P^(i)Pr₃, 5% 80° C., 18 h^(d) 95^(a) (5 of 11)

12 1,2,3-C₆F₄₃H₂₃ P^(i)Pr₃, 5% 80° C., 48 h 50^(a) (30 of 14)

13 1,2,3-C₆F₄₃H₂₃ P^(i)Pr₃, 5% 80° C., 18 h^(c) 30^(a) (40 of 13 andBu₆Sn₂)

14 1,3-C₆F₄₂H₂₄ P^(i)Pr₃, 5% 80° C., 18 h 90^(a)

15 1,2-C₆F₄₂H₂₄ P^(i)Pr₃, 5% 80° C., 72 h^(e) 92^(a) (2 of 17)

16 1,4-C₆F₄₂H₂₄ P^(i)Pr₃, 5% 80° C., 18 h^(e) 90^(a) (10 of 19)

18 2,3,5,6-C₆F₄HN P^(i)Pr₃, 5% 80° C., 2 h 98^(a) (87^(b))

22

FIGS. 1 and 2 provide the chemical equations for production of thespecific functionalized or stannylated fluorinated arene compoundsnumerically identified in Table 1 above. It has been discovered thatarene compounds with C—H bonds that are adjacent to two C—F bonds suchas 1,3-difluorobenzene, 1,2,4-trifluorobenzene, 1,3,5-trifluorobenzene,1,2,3,5-tetrafluorobenzene, 1,2,4,5-tetrafluorobenzene, andpentafluorobenzene are most reactive.

The monostannylated compounds 1, 2, 4, 7 and 10 were obtained with goodselectivity (above 91%) using a modest excess of the fluorinated arenecompound (about two times the molar amount); the only significantimpurities were the distannylated fluorinated arene compounds 3, 5, 8,and 11 which were readily separated. The distannylated fluorinated arenecompounds could be obtained with good selectivity by using 2.5 times themolar amount of Bu₃Sn(CH═CH₂). The tristannylated fluorinated arenecompound 13 was also accessible using P^(i)Pr₃ as the ancillary ligand.

Compared to data on similar or analogous functionalization by use ofboron chemistry as described above, the preferred functionalization ofthe present invention has been demonstrated to occur under milderconditions, produce higher yields, and be more selective, with no C—Ffunctionalization products observed.

Although use of P^(i)Pr₃ as the ancillary ligand has been observed toprovide lower reaction rates than that of MeNC₅H₄N^(i)Pr, P^(i)Pr₃ ispreferable when carrying out the functionalization at highertemperatures due to improved thermal stability. For example,functionalization of 1,2,3,4-tetrafluorobenzene occurred in 4 hours at80° C. and provided selective conversion to the monostannylatedfluorinated arene compound 6. Similar results were demonstrated with thefunctionalization of 1,2,3-trifluorobenzene, providing themonostannylated fluorinated arene compound 13. The distannylatedfluorinated arene compound 14 was also obtained selectively in thepresence of excess Bu₃Sn(CH═CH₂) and was present as a slight impurity inthe synthesis of the monostannylated fluorinated arene compound 13. Thefunctionalization of heterocycles such as 2,3,5,6-tetrafluoropyridinewas also demonstrated using an ancillary ligand comprising a phosphine.

Two plausible mechanistic manifolds for the preferred method offunctionalizing C₆F₅D with cis-(1-propenyl)SnBu₃ that invoke theoxidative addition product L₂NiD(C₆F₅), where L is the ancillary ligand,are shown in FIG. 3. One possibility is that the reaction occurs byoxidative addition of C—H and C—Sn bonds to Ni centers, pure σ-bondmetathesis, or some combination of these processes. An example of thismechanistic manifold showing oxidative addition of the C—H bond of thefluoroarene and σ-bond metathesis to form the new C—Sn bond is shown inFIG. 3 as mechanism A. In this mechanism, the double bond of thepropenyl group coordinates to the metal, which brings the Bu₃Sn and C₆F₅substituents into close enough proximity to undergo σ-bond metathesis.Reductive elimination of (Z)-1-deuteropropene followed by oxidativeaddition of C₆F₅D regenerates L₂NiD(C₆F₅). Mechanism B involves1,2-insertion of the vinyl moiety into the Ni-D bond followed byβ-elimination of the SnBu₃ group. Mechanism B would produce(E)-1-deuteropropene and thus can be differentiated from mechanism A.

Experimentally, the functionalization of C₆F₅D withcis-(1-propenyl)SnBu₃ was observed to liberate almost exclusively(Z)-1-deuteropropene at 50% conversion, as identified by ¹H NMRspectroscopy. The formation of (Z)-1-deuteropropene supports mechanisticmanifold A, where oxidative addition, σ-bond metathesis, or acombination of these processes accounts for Sn—C bond formation.Mechanism A is reminiscent of Stille coupling, where the aryl group inthis case adopts the role typically played by a halide anion during thetransmetalation step. This reaction pathway provides an unexpected routeto C—H bond functionalization under mild conditions.

We claim:
 1. A method of functionalizing a C—H bond of an arene compoundcomprising the step of reacting a first organometallic compound withsaid arene compound in the presence of a catalyst, wherein: a. saidfirst organometallic compound comprises a group 14 element; and b. saidarene compound comprises at least one hydrogen bonded to a carbon. 2.The method of claim 1, wherein the method is carried out in a singlestep.
 3. The method of claim 1, wherein said first organometalliccompound is selected from the group consisting of an organotin compound,an organosilane compound, an organogermanium compound and an organoleadcompound.
 4. The method of claim 1, wherein said organometallic compoundcomprises an organotin compound having the chemical formula R₃SnR¹,wherein: a. each of said R is selected from the group consisting of amethyl group and a butyl group; and b. said R¹ comprises a double bond.5. The method of claim 4, wherein said double bond is adjacent to a bondbetween said R¹ and said Tin.
 6. The method of claim 5, wherein said R¹is selected from the group consisting of a vinyl group and a propenylgroup.
 7. The method of claim 6, wherein said organotin compound isselected from the group consisting of Me₃Sn(CH═CH₂), Bu₃Sn(CH═CH₂),Me₃Sn(CH═CHCH₃) and Bu₃Sn(CH═CHCH₃), wherein said Me is the methyl groupand said Bu is the butyl group.
 8. The method of claim 3, wherein saidorganosilane compound has the chemical formula R² ₃SnH, wherein each ofsaid R² is selected from the group consisting of a phenyl group and ahydrogen.
 9. The method of claim 4, wherein said arene compound is afluorinated heterocyclic compound.
 10. The method of claim 1, whereinsaid arene compound has as a substituent a fluorine.
 11. The method ofclaim 4, wherein said arene compound is benzene.
 12. The method of claim11, wherein said benzene has as a substituent a fluorine.
 13. The methodof claim 12, wherein said hydrogen is adjacent to two of said fluorine.14. The method of claim 12, wherein said benzene is selected from thegroup consisting of 1,2-difluorobenzene, 1,3-difluorobenzene,1,4-difluorobenzene, 1,2,3-trifluorobenzene, 1,2,4-trifluorobenzene,1,3,5-trifluorobenzene, 1,2,3,4-tetrafluorobenzene,1,2,3,5-tetrafluorobenzene, 1,2,4,5-tetrafluorobenzene, andpentafluorobenzene.
 15. The method of claim 1, wherein said catalystcomprises at least one of a second organometallic compound and anancillary ligand.
 16. The method of claim 15, wherein said secondorganometallic compound comprises an element selected from the groupconsisting of nickel and mercury.
 17. The method of claim 15, whereinsaid ancillary ligand comprises at least one of PCy₃, P^(i)Pr₃, PEt₃ andMeNC₅H₄N^(i)Pr, wherein said Cy is a cyclohexyl group; said ^(i)Pr is aisopropyl group; said Et is an ethyl group; said Me is a methyl group;and said MeNC₅H₄N^(i)Pr has the following structural formula:


18. The method of claim 17, wherein said second organometallic compoundcomprises Ni(COD)₂, wherein COD is 1,5-cyclootadiene.
 19. The method ofclaim 18, wherein said organometallic compound comprises an organotincompound having the chemical formula R₃SnR¹, wherein: a. each of said Ris selected from the group consisting of a methyl group and a butylgroup; and b. said R¹ comprises a double bond.
 20. The method of claim1, wherein said step is carried out with a first molar amount of saidreagent and a second molar amount of said organic compound, wherein saidfirst molar amount is stoichiometrically equivalent to said second molaramount.
 21. The method of claim 20, wherein said first molar amount isgreater than said second molar amount.
 22. The method of claim 20,wherein said first molar amount is less than said second molar amount.23. The method of claim 1, wherein said step is carried out at atemperature of between 25° C. to 45° C.